Even without exposure to the sun, redheads may be more at-risk for melanoma.

As a freckle-faced redhead, I’m constantly reminded to wear a hat and to slather myself with sunscreen. Even strangers on the street warn me to stay out of the sun. Unfortunately, I’m now faced with the fact that even these safeguards may not be enough to protect me from skin cancer. New research in Nature suggests redheads may be genetically predisposed to melanoma, even if they never see a ray of UV light.

Pigment production is controlled by a gene called MC1R, and is responsible for the veritable rainbow of human complexions. The relative abundance of two pigments (pheomelanin and eumelanin) determines hair and skin color. In dark-skinned individuals with dark hair, MC1R activity leads to production of large amounts of eumelanin, compared to relatively small amounts of pheomelanin. Redheads with fair skin have mutations that disrupt the MC1R pathway, producing more pheomelanin than eumelanin. We’ve long known that redheads are at a high risk of sun-induced skin cancer, but the researchers behind this study wondered whether something about pheomelanin itself may contribute to the high incidence of melanoma in those with fair skin, even in the absence of cancer-causing UV exposure.

To investigate this potential link, the researchers used strains of mice with pigment profiles that mimicked various human complexions. Like humans with dark skin, control mice with black coats had an intact MC1R gene and produced much more eumelanin than pheomelanin. A second strain of mice, with a mutated MC1R gene, had reddish coats and had a much higher pheomelanin to eumelanin ratio. The third strain of mice was albino, which produced no pigment at all.

Mice from each strain were then crossed with mice with a mutation called BRAFV600E, which has been implicated in the development of malignant melanoma. (Up to 60 percent of all human patients with melanoma have this mutation.) The researchers then monitored the mice over time, carefully making sure that they were not exposed to UV light or any other environmental cancer-causing agents.

Black and albino mice that carried the BRAFV600E mutation developed melanoma at a very low rate, and only after a long period of time. However, more than 50 percent of the red mice with the same mutation developed melanoma after just one year.

To determine whether pheomelanin itself was behind this extremely high incidence of cancer, the researchers halted pigment production in red mice by introducing an albino allele. After a year, melanoma incidence in these mice was no different than those in the black or albino mice, suggesting that something about the pheomelanin pathway itself may play a role in UV-independent melanoma.

It turns out that redheads may be vulnerable to more oxidative DNA damage, even if they stay out of the sun: the researchers found several indicators of DNA damage—lipid peroxide and two cyclopurine levels—were much higher in mice that produced large amounts of pheomelanin. This DNA damage, in turn, contributes to the development of malignant melanoma.

It has long been known that UV radiation causes skin cancer, especially in fair-skinned redheads, but these results suggest that even redheads that stay out of the sun aren’t completely protected from melanoma. The same pigment pathway that gives them their fiery hair and freckles may actually damage their DNA and lead to melanoma, without any help from the sun’s rays. Unfortunately, it’s still unclear how to stop this damage. Experts advise redheads to visit the dermatologist regularly, and suggest that increasing oral antioxidant intake might decrease melanoma risk.

But, of course, don’t throw away that sunscreen; sun exposure is still the leading risk factor for skin cancer, in both redheads and others.

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Kate Shaw Yoshida
Kate is a science writer for Ars Technica. She recently earned a dual Ph.D. in Zoology and Ecology, Evolutionary Biology and Behavior from Michigan State University, studying the social behavior of wild spotted hyenas. Emailkate.shaw@arstechnica.com//Twitter@KateYoshida

Interesting read for someone like me. I'm 1 step away from being a ginger: Light skin, freckles, lots of red and blonde in my beard, but dark black hair up top. In Eric Cartman terms, I wonder if that makes me a "Day Walker" or not... Anyways, I'm left wondering what it means for someone like me in context of the articles findings.

As far as I'm aware, there is little to no evidence for any benefit from taking antioxidant supplements in food. While the suggestion that increased anti-oxidant intake would help reduce oxidation-induced damage sounds logical, it's unknown what that increased intake does in a complicated soup of chemicals in our bodies.

Or is there now convincing, in vivo evidence that anti-oxidant intake does help?

I am red, and still young enough to not worry too much.. but then there's family history.

Grandfather on one side was red before the current grey. He's had several facial skin cancers, it's obvious he's had them in the past too.

Mother doesn't have red hair, but it's in the genes (obviously), and she's a blond. A couple minor melanoma that have been removed so far, also in the facial region (neck), before 50.

I don't know too many other older red haired people (maybe one other), but just from family history I can believe at least a disposition towards it based on skin color, and it wouldn't take too much for me to believe in a further disposition regardless of sun exposure because of my genes.

That's rather annoying, to have to know you're probably going to get something in the next twenty years, before you ever get a grey hair.

As annoying as that is, I then have to go: how much will this end up costing me? Is being a red head going to mean I can't get reasonable medical insurance because now having red hair is a pre-existing condition?

And to think I don't even need to be exposed to sunlight. Anyways, this all means something very important: anytime something on your skin changes (or if a mole or something that has always existed seems slightly larger... or even if it doesn't but you're getting older), check with the derm.

As far as I'm aware, there is little to no evidence for any benefit from taking antioxidant supplements in food. While the suggestion that increased anti-oxidant intake would help reduce oxidation-induced damage sounds logical, it's unknown what that increased intake does in a complicated soup of chemicals in our bodies.

Or is there now convincing, in vivo evidence that anti-oxidant intake does help?

The Vitamin A for smokers and lung cancer trial, which was using Vitamin A as an antioxidant had to be stopped early due to the increase in cancers seen. I believe the Vitamin E/selenium trial for prostate cancer showed absolutely no benefit other than to those selling Vitamin E and selenium.

Warning, personal opinion from a physician not an oncologist: There are no minor melanomas. Melanoma is a sneaky bastard. There are case reports of melanomas recurring in transplant recipients from donors having removal 32 years before:http://www.ncbi.nlm.nih.gov/pubmed/20451456

Despite the surface plausibility of taking reductive agents (vits ACE)and other supplements to prolong life we have little positive to say for this except for the above noted economic multiplier effect of spending your money. "Spend your money, support the economy. Save your money, support the economy." The Vit E supplements in coronary disease and cancer trial found no benefit for either but a higher rate of congestive heart failure and hospitalization for same. http://www.ncbi.nlm.nih.gov/pubmed/1576 ... t=Abstract

Many thoughtful authorities (and some experts like me,one step below an authority) suggest that there is a U shaped curve for many nutrient's intake vs health or longevity or goodness. Too low, life sucks; too high it sucks as well, just more subtly. Vitamin D may buck this trend but the jury is yet out.

'Maters are supposed to reduce prostate cancer risk but this fact did not affect my opposing genetics at age 50.

Bopper, one of a crew of three redheads with no melanomas and multiple skin cancers and grey hairs.

I have been 100% successful at treating all skin cancers and pre-cancerous lesions on my own body for four years, including six melanomas. The "miracle cure" that I have used is a compound called terpinen-4-ol, which is the active ingredient in tea tree oil. If you do a search, you will find a number of papers on research that has been done. This material works by dis-inhibiting cellular apoptosis. I have not had any surgery, radiation or chemotherapy. I have written two papers on my experience if anyone is interested.

Ireland has a preponderance of redheads. Many Irish were shipped to Australia as convicts. Why is it any wonder that Australians have some of the highest rates of skin cancer in the world?

Were they all shipped to the Gold Coast? Probably not, so maybe you were being tongue in cheek but I'm guessing that greater contributing factors are:

- Australia has an unusually high amount of sun, as far as I can tell- We have a strong beach culture. Note that skin cancer occurrence is highest in regions with strong beach cultures, such as the Gold Coast- The hole in the ozone layer over Antarctica gives Australia high exposure. It's true that other nations such as Chile, Argentina, South Africa etc might have similar issues, but I also doubt their beach culture is as dominant. On that matter, I might go and look up skin cancer rates among white South Africans.

I have been 100% successful at treating all skin cancers and pre-cancerous lesions on my own body for four years, including six melanomas. The "miracle cure" that I have used is a compound called terpinen-4-ol, which is the active ingredient in tea tree oil. If you do a search, you will find a number of papers on research that has been done. This material works by dis-inhibiting cellular apoptosis. I have not had any surgery, radiation or chemotherapy. I have written two papers on my experience if anyone is interested.

I would be fascinated to learn how you determined that these lesions were pre-cancerous or malignant in the absence of surgery. Standard practice is to remove suspicious lesions and test for malignancy - this requires surgery. Highly suspicious lesions are removed along with one or more sentinel nodes.

On the matter of the original article, I find this amazing - and a little spooky. I was talking to my partner about it yesterday when we were out for a walk with the dogs, and I asked about melanoma rates in albinos - neither of us knew. I was under the impression that it was equally dangerous for red heads and albinos, as I made the (obviously simplistic) assumption that skin cancer rates tended to be a function of eumelanin absorption of UV rays. I had no idea that pheomelanin was associated with chemicals that caused DNA damage in itself.

Does anyone know if - skin pigment aside - pheomelanin has any other functional effects? Eumelanin converts some 99% of absorbed UV radiation into heat as well as causing dark skin pigment - what about pheomelanin?

Interesting read for someone like me. I'm 1 step away from being a ginger: Light skin, freckles, lots of red and blonde in my beard, but dark black hair up top. In Eric Cartman terms, I wonder if that makes me a "Day Walker" or not... Anyways, I'm left wondering what it means for someone like me in context of the articles findings.

I have been 100% successful at treating all skin cancers and pre-cancerous lesions on my own body for four years, including six melanomas. The "miracle cure" that I have used is a compound called terpinen-4-ol, which is the active ingredient in tea tree oil. If you do a search, you will find a number of papers on research that has been done. This material works by dis-inhibiting cellular apoptosis. I have not had any surgery, radiation or chemotherapy. I have written two papers on my experience if anyone is interested.

Ireland has a preponderance of redheads. Many Irish were shipped to Australia as convicts. Why is it any wonder that Australians have some of the highest rates of skin cancer in the world?

Were they all shipped to the Gold Coast? Probably not, so maybe you were being tongue in cheek but I'm guessing that greater contributing factors are:

- Australia has an unusually high amount of sun, as far as I can tell- We have a strong beach culture. Note that skin cancer occurrence is highest in regions with strong beach cultures, such as the Gold Coast- The hole in the ozone layer over Antarctica gives Australia high exposure. It's true that other nations such as Chile, Argentina, South Africa etc might have similar issues, but I also doubt their beach culture is as dominant. On that matter, I might go and look up skin cancer rates among white South Africans.

Australia has sun problems that make it bad for basically any variety of light-skinned individual, yes.

But that doesn't really evade the fact that the primary genetic background of Australia's European "colonists" was Irish. My mother's family tree looks like this: ruling family of County Monaghan, Protestant converts (disowned, re-acknowledged, disowned...and I think still disowned), Australian penal colonists, American Civil War era military conscripts, British house servants, successful entrepreneurs in both Britain and America (and Australia, incidentally). More or less in that order.

Fortunately, like one of the above posters, my other ethnic heritages offset the ginger and I just have to deal with having a red-blonde beard, although (and this goes for the other gentleman) I have to remember that I can still have redheaded kids because it's a surprisingly insidious recessive gene shared by virtually everyone with Celtic or Scandinavian ancestry.

I'd be interested to see a study determining whether redheads are better at taking in Vitamin D in less sunny climes (than other light-skinned people). I'd be willing to bet on the outcome of that study, too.

It isn't just redheads though. My whole family is of Gaelic decent. But not a redhead in the bunch, yet high rates of skin cancers. It has caused me to shun beaches like there is no tomorrow! Most in my family do. And we wear long sleeves during the summer!

But a warning: just because your skin isn't pale doesn't mean you have a magical immunity to skin cancer! Take it seriously, and use sun block. No one should ever have to go through cancer treatment, it is horrible and scaring. I speak from experience (four tumors removed from my stomach).

And remember: We're entering the winter, and sun reflection of off snow and ice can also cause burns and over exposure to UV radiation! So please be careful out there, even if it's cold outside!

I can't even imagine what it's like to be a redhead and just deal with sun exposure let alone something like this.

My wife is pretty damn pale, her family comes from Ireland. She's not a redhead but direct sunlight can lightly burn her in 20 minutes or so. How fast does a true redhead burn!

I recently moved from the southern US to the UK. After moving here, I figured that I wouldn't need to make as much of a conscious effort to wear sunscreen and/or a hat when I was outside as I did in Alabama, where if I was out for more then an hour (even in November) I had to wear sunscreen and/or a head covering. I was playing a concert at a town fair near Manchester, and was outside for probably 2 hours or so in direct sunlight. I managed to get sunburnt on the top of my head.

So, redheads can get sunburnt... in Manchester, UK... in September... in less then 2 hours. Needless to say, I felt a bit silly about that.

I'm certainly watching most of the moles that already exist, and will have to continue to do so for the rest of my life. Goes with the territory.

I come from a Dutch family with some particularly strong redheaded genes. My uncle who is not a redhead, married an Italian woman and proceeded to have three boys, two of which were redheads and one who actually looked Italian. My mother and half brother are redheads. I am not, but have the fair skin (and predilection to burn) and lots of red hairs (but not full head of) in my beard and hair.

I'm curious how far and long the mutation goes. With my family history, I suspect I would be likely to have redheaded spawn. Which leads me to think that I probably carry enough of the redheaded gene mutation to worry about the day star.

As a redhead myself this is rather depressing to read. Well, time to get my ass to a dermatologist on the regular. And harass my Dad into it as well.

As for burning in the sun, I give it ten minutes of solid exposure and then it starts turning red. Some days it literally hurts to be out in direct sun for more than a couple of minutes, it results in such an intense burning sensation. Those heat treatment zit thingos dont work on me either, unless by working you mean "Hurts like hell and makes my skin madder".

I can't even imagine what it's like to be a redhead and just deal with sun exposure let alone something like this.

My wife is pretty damn pale, her family comes from Ireland. She's not a redhead but direct sunlight can lightly burn her in 20 minutes or so. How fast does a true redhead burn!

I recently moved from the southern US to the UK. After moving here, I figured that I wouldn't need to make as much of a conscious effort to wear sunscreen and/or a hat when I was outside as I did in Alabama, where if I was out for more then an hour (even in November) I had to wear sunscreen and/or a head covering. I was playing a concert at a town fair near Manchester, and was outside for probably 2 hours or so in direct sunlight. I managed to get sunburnt on the top of my head.

So, redheads can get sunburnt... in Manchester, UK... in September... in less then 2 hours. Needless to say, I felt a bit silly about that.

I'm certainly watching most of the moles that already exist, and will have to continue to do so for the rest of my life. Goes with the territory.

That was indeed silly. LOL. I always figured that sun was sun but the difference between the UK and Alabama would be the average amount sunlight over the year, more then the intensity of the sun.

My wife seems to be a counter to this: Scots ancestry, flame red hair, (up top and down below) blue eyes, but her skin is not milk-white and tans "normally" in the manner of most white people. She almost never gets a sunburn and in fact between us both, I have the paler skin and burn easier, dispite French/Basque ancestry and dark hair. Anyway, she usually has nut-brown skin by the end of the summer, and no sign of skin cancer or even excessive moles on her.